Activity of β-galactosidase at pH 6 is a classic maker of senescence in cellular biology. Cellular senescence, a state of highly stable cell cycle arrest, is often compared to apoptosis as an intrinsic tumor suppression mechanism. It is also thought that SA-β-gal is crucial in malignant cell transformation. High levels of senescence-associated β-galactosidase (SA-β-gal) can be found in cancer and benign lesions of various localizations making the enzyme a highly promising diagnostic marker for visualization of tumor margins and metastases. These findings facilitate the research of therapy induced senescence as a promising therapeutic strategy. In this review, we address the need to collect and analyze the bulk of clinical and biological data on SA-β-gal mechanisms of action to support wider implementation of this enzyme in medical diagnostics. The review will be of interest to pathologists, biologists, and biotechnologists investigating cellular senescence for purposes of regenerative medicine and oncology.

A non-surgical pharmacological approach to control cellular vitality and functionality during ischemic and/or reperfusion-induced phases of strokes remains extremely important. The synthesis of 2-ethyl-6-methyl-3-hydroxypyridinium gammalactone-2,3-dehydro-L-gulonate (3-EA) was performed using a topochemical reaction. The cell-protective effects of 3-EA were studied on a model of glutamate excitotoxicity (GluTox) and glucose-oxygen deprivation (OGD) in a culture of NMRI mice cortical cells. Ca²⁺ dynamics was studied using fluorescent bioimaging and a Fura-2 probe, cell viability was assessed using cytochemical staining with propidium iodide, and gene expression was assessed by a real-time polymerase chain reaction. The compound anti-ischemic efficacy in vivo was evaluated on a model of irreversible middle cerebral artery (MCA) occlusion in Sprague-Dawley male rats. Brain morphological changes and antioxidant capacity were assessed one week after the pathology onset. The severity of neurological disorder was evaluated dynamically. 3-EA suppressed cortical cell death in a dose-dependent manner under the excitotoxic effect of glutamate and ischemia/reoxygenation. Pre-incubation of cerebral cortex cells with 10–100 µM 3-EA led to significant stagnation in Ca²⁺ concentration in a cytosol ([Ca2+]i) of neurons and astrocytes suffering GluTox and OGD. Decreasing intracellular Ca²⁺ and establishing a lower [Ca2+]i baseline inhibited necrotic cell death in an acute experiment. The mechanism of 3-EA cytoprotective action involved changes in the baseline and ischemia/reoxygenation-induced expression of genes encoding anti-apoptotic proteins and proteins of the oxidative status; this led to inhibition of the late irreversible stages of apoptosis. Incubation of brain cortex cells with 3-EA induced an overexpression of the anti-apoptotic genes BCL-2, STAT3, and SOCS3, whereas the expression of genes regulating necrosis and inflammation (TRAIL, MLKL, Cas-1, Cas-3, IL-1β and TNFa) were suppressed. 3-EA 18.0 mg/kg intravenous daily administration for 7 days following MCA occlusion preserved rats’ cortex neuron population, decreased the severity of neurological deficit, and spared antioxidant capacity of damaged tissues. 3-EA demonstrated proven short-term anti-ischemic activity in vivo and in vitro, which can be associated with antioxidant activity and the ability to target necrotic and apoptotic death. The compound may be considered a potential neuroprotective molecule for further pre-clinical investigation.

Nitric oxide (NO) is a gaseous molecule which plays a key role in wound healing. Previously, we identified the optimal conditions for wound healing strategies using NO donors and an air plasma generator. The aim of this study was to compare the wound healing effects of binuclear dinitrosyl iron complexes with glutathione (B-DNIC-GSH) and NO-containing gas flow (NO-CGF) at their optimal NO doses (0.04 mmol for B-DNIC-GSH and 1.0 mmol for NO-CGF per 1 cm²) in a rat full-thickness wound model over a 3-week period. Excised wound tissues were studied by light and transmission electron microscopy and immunohistochemical, morphometrical and statistical methods. Both treatments had an identical stimulating impact on wound healing, which indicated a higher dosage effectiveness of B-DNIC-GSH compared to the NO-CGF. B-DNIC-GSH spray application reduced inflammation and promoted fibroblast proliferation, angiogenesis and the growth of granulation tissue during the first 4 days after injury. However, prolonged NO spray effects were mild compared to NO-CGF. Future studies should determine the optimal B-DNIC-GSH solution course for a more effective wound healing stimulation.

The overall goal of regenerative medicine is to restore the functional performance of the tissues and organs that have been severely damaged or lost due to traumas and diseases

Клеточное старение - реакция клеток на повреждение в виде стойкого выхода из клеточного цикла, изменение активности сигнальных путей и секреторной активности, ассоциированных со старением. В зависимости от индуцирующего фактора выделяют несколько видов клеточного старения, однако независимо от причины, вызвавшей данный процесс, они имеют схожий морфологический и молекулярный профиль. Целью данного обзора явилась систематизация научных данных о молекулярных и морфологических механизмах клеточного старения. Материал и методы: проведен анализ основных зарубежных и отечественных источников по базам данных PubMed/ Medline, РИНЦ/elibrary. Заключение. Стареющие клетки секретируют ряд биологически активных веществ, которые, действуя краткосрочно, способствуют пролиферации клеток и регенерации органов и тканей. Длительное присутствие этих клеток, наоборот, способствует ингибированию пролиферации и синтетической активности клеток, поддержанию провоспалительной среды, что негативно отражается на структуре и функции тканей, приводит к развитию хронических заболеваний, в том числе атеросклероза, гипертонической болезни, остеоартрита и других, а также онкологии. Обнаружение стареющих клеток в тканях затруднено в связи с отсутствием характерной морфологии этих клеток при проведении стандартной световой микроскопии и требует проведения комплексных гистохимических и иммуногистохимических исследований с использованием нескольких антител. В настоящее время активно изучаются различные способы регуляции числа и секреторной активности стареющих клеток. Можно выделить два основных направления: сенолитическая и сеноморфная терапия. Первая направлена на селективное инициирование апоптоза в стареющих клетках, вторая - на снижение синтетической активности в них. Клеточное старение, независимо от инициирующего фактора, имеет схожие морфологические, биохимические и молекулярные изменениями со стороны подверженных ему клеток и оказывает серьезное воздействие на тканевые структуры. Углубление знаний о клеточном старении позволит разработать универсальные патогенетические препараты для профилактики и лечения множества заболеваний, при которых наблюдается персистирование клеток с фенотипом...

Objective. The current study aimed to compare the quality of tissue connection in flap plastic surgery using laser exposure and a traditional surgical suture in the experiment. Material and methods. The experiment was conducted in male Wistar rats. Skin defect was modeled on the withers. The hair was removed, followed by skin excision and closure with skin flaps according to Grose and Werner method. Eighteen laboratory animals were divided into 2 groups, each group contained 9 animals: 1 — control with plastic surgery with counter flaps, performed by connecting the edges of the wound with single-row interrupted sutures, 2 — experimental with plastic surgery with counter flaps, connected with biological solder under the laser radiation. The gadget for laser connection of biological tissues was provided by the Laboratory of Biomedical Nanotechnologies of the Institute of Biomedical Systems of the National Research University. On days 7, 14 and 21, the animals were sacrificed; the tensile strength of the suture, the morphology, and cosmetic characteristics of the wound were examined. Results. Local application of laser exposure with auxiliary materials of biological solder based on bovine serum albumin, collagen, indocyanine green, single-walled carbon nanotubes, and water did not cause mortality of animals in the groups. On day 7, the tensile strength yielded to the interrupted joint and amounted to 1.8±0.2 MPa, while by day 14 it amounted to 3.2±0.5 MPa and was comparable to the interrupted suture 3.4±0.5 MPa, respectively. Regarding the cosmetic characteristics of the scar on the SCAR scale on day 21, the total score for the nodal connection with skin grafting was 4 points, while with the laser connection it was 1. Conclusions. In plastic surgery, laser connection of wound edges with opposing flaps does not yield to the nodal connection in healing time of the surgical wound and strength on day 14. Also, it reduces the area of the scar and improves the cosmetic characteristics of the postoperative region on day 21.